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Biomedical subjects

P Clarkson

Publications and source records attributed to P Clarkson.

At least 19 recordsLinked to original sources
PubMed1997

Association of angiotensin-converting enzyme gene I/D polymorphism with change in left ventricular mass in response to physical training.

BACKGROUND: The absence (deletion allele [D]) of a 287-base pair marker in the ACE gene is associated with higher ACE levels than its presence (insertion allele [I]). If renin-angiotensin systems regulate left ventricular (LV) growth, then individuals of DD genotype might show a greater hypertrophic response than those of II genotype. We tested this hypothesis by studying exercise-induced LV hypertrophy. METHODS AND RESULTS: Echocardiographically determined LV dimensions and mass (n=140), electrocardiographically determined LV mass and frequency of LV hypertrophy (LVH) (n=121), and plasma brain natriuretic peptide (BNP) levels (n=49) were compared at the start and end of a 10-week physical training period in male Caucasian military recruits. Septal and posterior wall thicknesses increased with training, and LV mass increased by 18% (all P<.0001). Response magnitude was strongly associated with ACE genotype: mean LV mass altered by +2.0, +38.5, and +42.3 g in II, ID and DD, respectively (P<.0001). The prevalence of electrocardiographically defined LVH rose significantly only among those of DD genotype (from 6 of 24 before training to 11 of 24 after training, P<.01). Plasma brain natriuretic peptide levels rose by 56.0 and 11.5 pg/mL for DD and II, respectively (P<.001). CONCLUSIONS: Exercise-induced LV growth in young males is strongly associated with the ACE I/D polymorphism.

Adult↗
PubMed1997

Non-invasive measurement of endothelial function: effect on brachial artery dilatation of graded endothelial dependent and independent stimuli.

OBJECTIVE: To examine the relation between endothelial dependent and endothelial independent stimuli of varying intensity and measures of vascular function in the brachial artery of young healthy adults, to determine whether these responses are consistent and can be used to assess endothelial function. DESIGN AND SETTING: High resolution ultrasound was used to measure brachial artery diameter at rest, after reactive hyperaemia induced by forearm cuff occlusion, and after sublingual isosorbide dinitrate (ISDN). Each subject was assigned to a random order of six cuff occlusion times (30 seconds, 1.5, 2.5, 3.5, 4.5, and 8 minutes) and six doses of ISDN (10, 20, 50, 100, 200, and 400 micrograms). SUBJECTS: Three males and three females mean age 31 years (range 25 to 43) with no known risk factors for cardiovascular disease. MAIN OUTCOME MEASURES: Flow mediated, endothelial dependent dilatation was compared to duration of cuff occlusion, peak reactive hyperaemia, and duration of increased flow. Nitrate induced, endothelial independent dilatation was compared to dose of ISDN and change in flow. RESULTS: Vessel dilatation and duration of peak flow change increased with longer duration of cuff occlusion. After 4.5 minutes of occlusion, flow mediated dilatation was mean (SD) 96 (6)% of maximal response and did not increase significantly with longer occlusion times. No significant dilatation occurred after 10 or 20 micrograms of ISDN in any subject. With increasing doses up to 200 micrograms there was an increase in dilatation. Endothelial independent dilatation did not increase significantly with doses of ISDN above 200 micrograms. CONCLUSIONS: Measures of arterial function vary with duration of blood flow occlusion and ISDN dose. Maximum arterial response was reached in all subjects after 4.5 minutes of blood flow occlusion or 200 micrograms of ISDN. Therefore, these variables produce consistent reproducible measures of endothelial function.

Adult↗
PubMed1997

Interassay differences in growth hormone measurement in acromegaly.

We measured plasma growth hormone concentrations by three different two-site immunometric assays (Pharmacia hGH RIA, IDS Gamma-BCT and Delfia 22 kDa hGH) to determine whether there are GH isoforms secreted by acromegalic patients that are under-recognized by some assays. There was a fairly good agreement between assays with the IDS Gamma-BCT and Delfia 22 kDa assays giving lower results than the Pharmacia IRMA. GH was measured on stored plasma samples from 24 patients with proven acromegaly. There was a consistent difference between the three assays of approximately 20% of the mean value for each patient.

Acromegaly↗
PubMed1996

Endothelial dysfunction late after Kawasaki disease.

BACKGROUND: Kawasaki disease (KD) is a systemic vasculitis of childhood with widespread vascular endothelial damage in the acute stage. Long-term complications, such as myocardial infarction and death, are recognized, but the extent and nature of late vascular abnormalities that might predispose to these events have not been studied. METHODS AND RESULTS: We used high-resolution ultrasound to study endothelial function in the brachial artery of 20 patients 5 to 17 years after acute KD (median, 11 years) and compared findings with those in 20 age- and sex-matched control subjects. Vascular responses to reactive hyperemia (with flow increase leading to endothelium-dependent dilation) and to sublingual glyceryl trinitrate (GTN; endothelium-independent dilation) were recorded. The relationship between endothelium-dependent vascular responses and features of the endothelium acute illness was examined. There was no difference in baseline vessel diameter, degree of reactive hyperemia, or response to GTN between patients and control subjects. In contrast, flow-mediated dilation was markedly reduced in KD patients compared with control subjects (3.1% versus 9.4%; P < .001). Late endothelium-dependent responses were not related to features of the acute illness. CONCLUSIONS: Abnormalities of systemic endothelial function are present many years after resolution of acute KD, even in patients without detectable early coronary artery involvement. Because this may be an important factor in the genesis of late vascular complications, long-term follow-up of all patients with KD is indicated.

Adolescent↗
PubMed1996

Oral L-arginine improves endothelium-dependent dilation in hypercholesterolemic young adults.

In hypercholesterolemic rabbits, oral L-arginine (the substrate for endothelium derived nitric oxide) attenuates endothelial dysfunction and atheroma formation, but the effect in hypercholesterolemic humans is unknown. Using high resolution external ultrasound, we studied arterial physiology in 27 hypercholesterolemic subjects aged 29+/-5 (19-40) years, with known endothelial dysfunction and LDL-cholesterol levels of 238+/-43 mg/dl. Each subject was studied before and after 4 wk of L-arginine (7 grams x 3/day) or placebo powder, with 4 wk washout, in a randomized double-blind crossover study. Brachial artery diameter was measured at rest, during increased flow (causing endothelium-dependent dilation, EDD) and after sublingual glyceryl trinitrate (causing endothelium-independent dilation). After oral L-arginine, plasma L-arginine levels rose from 115+/-103 to 231+/-125 micromol/liter (P<0.001), and EDD improved from 1.7+/-1.3 to 5.6+/-3.0% (P<0.001). In contrast there was no significant change in response to glyceryl trinitrate. After placebo there were no changes in endothelium-dependent or independent vascular responses. Lipid levels were unchanged after L-arginine and placebo. Dietary supplementation with L-arginine significantly improves EDD in hypercholesterolemic young adults, and this may impact favorably on the atherogenic process.

Administration, Oral↗
PubMed1996

Passive smoking and impaired endothelium-dependent arterial dilatation in healthy young adults.

BACKGROUND: Passive smoking has been linked to an increased risk of dying from atherosclerotic heart disease. Since endothelial dysfunction is an early feature of atherogenesis and occurs in young adults who actively smoke cigarettes, we hypothesized that passive smoking might also be associated with endothelial damage in healthy young-adult nonsmokers. METHODS: We studied 78 healthy subjects (39 men and 39 women) 15 to 30 years of age (mean +/- SD, 22 +/- 4): 26 control subjects who had never smoked or had regular exposure to environmental tobacco smoke, 26 who had never smoked but had been exposed to environmental tobacco smoke for at least one hour daily for three or more years, and 26 active smokers. Using ultrasonography, we measured the brachial-artery diameter under base-line conditions, during reactive hyperemia (with flow increase causing endothelium-dependent dilatation), and after sublingual administration of nitroglycerin (an endothelium-independent dilator). RESULTS: Flow-mediated dilatation was observed in all control subjects (8.2 +/- 3.1 percent; range, 2.1 to 16.7) but was significantly impaired in the passive smokers (3.1 +/- 2.7 percent; range, 0 to 9; P < 0.001 for the comparison with the controls) and in the active smokers (4.4 +/- 3.1 percent; range, 0 to 10; P < 0.001 for the comparison with the controls; P = 0.48 for the comparison with the passive smokers). In the passive smokers, there was an inverse relation between the intensity of exposure to tobacco smoke and flow-mediated dilatation (r = -0.67, P < 0.001). In contrast, dilatation induced by nitroglycerin was similar in all groups. CONCLUSIONS: Passive smoking is associated with dose-related impairment of endothelium-dependent dilatation in healthy young adults, suggesting early arterial damage.

Adolescent↗
PubMed1996

Impaired vascular reactivity in insulin-dependent diabetes mellitus is related to disease duration and low density lipoprotein cholesterol levels.

OBJECTIVES: This study sought to examine whether endothelial function is impaired in the large vessels of asymptomatic young adults with insulin-dependent diabetes and whether endothelial dysfunction is related to duration or control of diabetes, small-vessel disease or other vascular risk factors. BACKGROUND: Endothelial dysfunction is an early event in atherosclerosis, and large-vessel atherosclerotic disease is the major cause of morbidity and mortality in diabetes. METHODS: We compared 80 young adults with insulin-dependent diabetes (15 to 40 years old; mean [+/- SD] diabetes duration 13 +/- 8 years) with 80 matched nondiabetic control subjects. Using high resolution vascular ultrasound, we measured brachial artery responses to reactive hyperemia (with increased flow causing endothelium-dependent dilation) and sublingual glyceryltrinitrate (causing endothelium-independent dilation). RESULTS: Flow-mediated dilation was significantly impaired in diabetic subjects (5.0 +/- 3.7% vs. 9.3 +/- 3.8% in control subjects, p < 0.001). The ratio of flow-mediated dilation to glyceryltrinitrate-induced dilation was significantly lower in the diabetic subjects (p < 0.02), indicating that impaired dilation to increased flow was out of proportion to the impairment of the glyceryltrinitrate response in these subjects (15.6 +/- 5.6% vs. 19.7 +/- 6.6% in control subjects, p < 0.001). On multivariate analysis, flow-mediated dilation was inversely related to both duration of diabetes (r = -0.26, p < 0.05) and low density lipoprotein (LDL) cholesterol levels (r = -0.38, p < 0.005). CONCLUSIONS: Vascular reactivity is impaired in the systemic arteries of asymptomatic young adults with insulin-dependent diabetes and may represent early large-vessel disease. The degree of impairment is related to the duration of diabetes, and these patients appear particularly vulnerable to damage from LDL cholesterol, even at levels considered acceptable in nondiabetic subjects.

Adolescent↗
PubMed1996

The acute rise in plasma fibrinogen concentration with exercise is influenced by the G-453-A polymorphism of the beta-fibrinogen gene.

We have investigated the effects of chronic physical training and acute intensive exercise on plasma fibrinogen levels and the relationship of these responses to beta-fibrinogen G-453-A polymorphism genotype. One hundred fifty-six male British Army recruits were studied at the start of their 10-week basic training, which emphasizes physical fitness. Cohorts were restudied between 0.5 and 5 days after a major 2-day strenuous military exercise (ME) undertaken in their final week of training. Changes in fibrinogen concentration were adjusted for the effects of age, body mass index, and smoking history. Compared with baseline values, fibrinogen concentrations were significantly lower (11.9%, P=.04) at day 5 after ME, consistent with the beneficial effect of training. However, they were higher on days 1 through 3 after ME (suggesting an "acute-phase" response to strenuous exercise) and were maximal on days 1 and 2 (27.2%, P<.001 and 37.1%, P<.001 respectively). Fibrinogen genotype was available in 149 individuals. As expected from previous studies, men with one or more fibrinogen gene A-453 alleles had plasma fibrinogen concentration slightly but significantly higher at baseline (4.5%, P=.11). During the acute-phase response (days 2 and 3), however, the degree of rise was strongly related to the presence of the A allele, being 26.7+/-5.4% (mean+/-SE), 36.5+/-11.0%, and 89.2+/-30.7 for the GG, GA, and AA genotypes, respectively (P=.01). These results confirm that chronic exercise training lowers plasma fibrinogen levels, that intensive exercise generates an acute-phase rise in levels, and that this acute response is strongly influenced by the G/A polymorphism of the beta-fibrinogen gene.

Adolescent↗
PubMed1995

Localisation of androgen receptors in dermal fibroblasts, grown in vitro, from normal subjects and from patients with androgen insensitivity syndrome.

Human genital skin fibroblasts show the androgen receptor (AR) as bright red granules (0.5 micron in diameter) after treatment with one (of 3) primary polyclonal antibody and a secondary antibody linked to alkaline phosphatase. Almost all AR were cytoplasmic in 12 normal strains and in 8 strains from patients with partial (PAIS) and 6 with complete androgen insensitivity syndrome (CAIS). When 25.8 nM 5-alpha-dihydrotestosterone (DHT) or methyltrienolone was added to the medium, some AR were translocated into the nucleus in 13 experiments with 8 strains of normal fibroblasts; of 8 strains of patients with PAIS 3 failed to translocate to a detectable extent in the presence of androgen in the medium and none of the 6 strains from patients with CAIS translocated.

Androgens↗
PubMed1995

Wide diversity in measurements of growth hormone after stimulation tests in short children are due to assay variability.

A comparison of three commercially available assays for growth hormone (Pharmacia hGH RIA, IDS Gamma-BCT GH and Delfia 22 kDa hGH) were used to measure growth hormone (GH) secretion in 26 short children after pharmacological stimulation. The IDS Gamma-BCT assay was compared with Pharmacia assay in 15 provocative tests (13 children; n = 94). The Pharmacia assay showed a strong positive proportional bias and this was particularly marked at GH > 20 mU/L; the mean difference between the assays at GH < 10 mU/L was 12%. The IDS Gamma-BCT assay was also compared with the Delfia 22 kDa assay in 18 provocative tests (13 children; n = 100). Results from the IDS assay was higher throughout the range 0-90 mU/L with a mean difference of 11.4% in the range 10-90 mU/L; the mean difference between the assays at GH < 10 mU/L was -39%.

Child↗
PubMed1994

Diastolic heart failure.

Diastolic heart disease is common and appears to be the primary abnormality in a substantial proportion of all patients with CHF. The epidemiology and natural history of the condition appears different to that of systolic heart failure, resulting in significant morbidity although contributing little to overall mortality. Clinical assessment alone is inadequate to distinguish systolic from diastolic failure, and echocardiography is an essential investigation in the management of these patients. From a therapeutic standpoint an alternative approach to treatment is likely to be indicated, and the results of recent major trials in systolic heart failure cannot necessarily be extrapolated to this group of patients.

Adrenergic beta-Antagonists↗
PubMed1994

Expression of BCL-2 in the developing human fetal and infant breast.

The expression of BCL-2 protein was analysed in 10 fetal and 45 infant breast specimens by immunocytochemical staining of methacarn-fixed, paraffin-embedded tissue. In the developing fetal breast bud, BCL-2 was expressed in the basal cell layer and in the surrounding mesenchyme. Basal cells of epithelial buds destined to become hair follicles also expressed BCL-2 while the basal cell layer of the epidermis was negative. In infant breasts studied (aged 0-2 years), there was heterogeneous staining of the luminal epithelial cells of the ducts and lobules and no staining of myoepithelial cells or fibroblasts. The intensity of staining had a strong positive correlation with the age of the infant. Although the function of the bcl-2 gene in epithelial cells is unknown, these findings suggest that bcl-2 has a role in the morphogenesis of the human breast, and may help to sustain active epithelial-mesenchymal interaction by inducing longevity of certain cells.

Breast↗
PubMed1994

Doppler echocardiography and the early diagnosis of carditis in acute rheumatic fever.

BACKGROUND: The incidence of acute rheumatic fever in New Zealand remains relatively high. Reliable early diagnosis of carditis is difficult and important in management. AIM: To determine if Doppler echocardiography contributed to the early diagnosis of carditis in acute rheumatic fever. METHODS: Forty-seven patients admitted to hospital with suspected acute rheumatic fever and 19 control patients, with a febrile illness due to a documented non-cardiac bacterial infection, were assessed two days and two weeks following admission. Presence or absence of clinical carditis was determined by a cardiologist unaware of the suspected diagnosis, from clinical examination, chest radiograph, electrocardiogram (ECG) and two dimensional echocardiogram. Doppler echocardiography was then performed and interpreted by a second cardiologist unaware of the diagnosis. After completion of the study the Jones criteria were applied, to categorise the patients with suspected acute rheumatic fever into four groups for the final diagnosis: no acute rheumatic fever, possible acute rheumatic fever, definite acute rheumatic fever without carditis, and definite acute rheumatic fever with carditis. RESULTS: In 19 patients with a final diagnosis of acute rheumatic fever and carditis at the baseline assessment carditis was detected by clinical assessment in 15 patients, compared with 19 patients with evidence of significant valve regurgitation by Doppler echocardiography. Following the two week assessment, all 19 patients had both clinical and Doppler evidence of carditis. Five patients with a final clinical diagnosis of possible acute rheumatic fever or definite acute rheumatic fever without carditis, had a Doppler abnormality detected. There was no clinical or Doppler abnormality in the febrile controls. CONCLUSIONS: Doppler echocardiography is more sensitive than clinical assessment in the detection of carditis in acute rheumatic fever, and can contribute to earlier diagnosis.

Acute Disease↗
PubMed1994

Effect of ethnic origin of mother on fetal outcome.

The outcome of 11046 infants, from 20 weeks' gestation, born to mothers of different ethnic origins within one London borough has been analysed. There was no difference in perinatal death rates between the Asian and white infants. Among those with mothers from Africa and the West Indies there were overall significantly more intrauterine deaths (26.8/1000 and 20.0/1000) and neonatal deaths (8.6/1000 and 9.6/1000) than for the white mothers (intrauterine deaths 8.3/1000; neonatal deaths 3.7/1000). At less than 28 weeks', gestation specific death rates were similar in all groups and the overall higher death rates were due to an increase in the proportion of preterm deliveries among the black mothers. From 28 to 36 weeks' gestation, black infants born alive had lower neonatal death rates (7.7/1000) than the white infants (19/1000). The cause of the increased incidence of preterm labour among the black mothers is uncertain, though differences in intrauterine infection rates may be an important factor.

Adult↗
PubMed1994

Left ventricular hypertrophy in hypertension--general and local trends in diagnosis and therapy.

LVH is a frequent echocardiographic finding in the general population but it should be regarded as an ominous predictor of future cardiovascular events rather than an innocent compensatory phenomenon. Echocardiography is the most sensitive and specific method for its detection but the ECG should not be regarded as superfluous since additional prognostic information and information about coexisting myocardial damage is present. The decreasing prevalence of LVH suggests that LVH can be prevented by control of hypertension and prevention of weight gain. Once LVH is present then antihypertensive drugs, weight reduction or salt restriction may promote its reversal, with early studies demonstrating associated improvement in mortality and morbidity.

Adult↗
PubMed1994

Left ventricular diastolic dysfunction.

Diastolic heart failure is common, particularly in patients with coronary artery disease and hypertension. Although it does not contribute to heart failure mortality to the same degree as systolic dysfunction, it is responsible for significant morbidity. Clinical suspicion is a prerequisite to the diagnosis, which should be considered in all patients with exercise intolerance due to dyspnoea, particularly if associated with a history of ischaemic heart disease or hypertension. Although invasive haemodynamic studies are the gold standard investigation, this method of assessment is limited to a very small proportion of these patients, and echocardiography remains the single most useful investigation. It is important to realize that the management of diastolic heart disease depends to a large extent on the aetiology, which contrasts with the treatment of systolic dysfunction. As indicated, a wide variety of different drugs may potentially be of benefit, although considerable further research will be needed to more clearly define this heterogenous condition and its optimal treatment.

Diastole↗